1. ¹Molecular Medicine and Gene Therapy Unit, Room 1.302 Stopford Building, University of Manchester, Oxford Road, Manchester, M13 9PT, UK
2. ^†Gene Therapeutics Research Institute, Research Pavillion, Room 5093, 8700 Beverly Blvd., Los Angeles, California, 90048, USA

Correspondence: Maria G. Castro, Fax: (310) 423-0225. E-mail: lowensteinp@cshs.org, castromg@cshs.org.

^*Present address: Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, Washington 98195, USA

Received 26 March 2001; Accepted 21 September 2001.

Abstract

One of the challenges of neurological gene therapy for the treatment of chronic neurodegener-ative disorders, such as Parkinson's and Alzheimer's diseases, is achieving high levels, widespread distribution, and long-lived transgene expression in the brain. Here, following the intracerebral injection of a recombinant adenovirus (RAd) encoding herpes simplex virus type 1 thymidine kinase (HSV1-TK), we detect very high levels of HSV1-TK immunoreactivity throughout the brain both ipsilaterally and contralaterally to the injection site, for up to 12 months following vector administration. This study concludes that long-term, high-level, and anatomically distributed HSV1-TK immunoreactivity can be obtained, and that this is most likely due to transgene-specific properties, because neither the distribution nor the longevity were observed for the transgene -galactosidase encoded by a co-injected vector. Thus, we demonstrate that transgene expression can be achieved over widespread areas of the rodent brain, even 12 months after a single injection of first-generation adenovirus vector.